The central hypothesis of the proposal is that interneurons localized in the stratum lacunosum moleculare (SLM Is) in hippocampal area CAS are capable of expressing mossy fiber long-term potentiation (MF LTP). The central hypothesis will be tested with whole-cell recordings from SLM Is, anatomical labeling, and electrical stimulation of MF and PP pathways. These investigations will address the following two Specific Aims. Aim 1: To identify the requirements for the induction and maintenance of LTP at MF to SLM I synapses in area CAS of the hippocampus. More specifically, we will test the following hypotheses: a) LTP at MF to SLM I synapses is mediated by postsynaptic Ca2+ via activation of group I mGluR receptors; b) LTP at MF to SLM I synapses is mediated by PKA and PKC activation; and c) The early maintenance phase of LTP at MF to SLM I synapses depends on protein synthesis. Aim 2: To examine the changes in efficacy of synaptic integration in SLM I produced by LTP induction at MF to SLM I synapses in area CAS of the hippocampus. More specifically, we will test the following hypotheses: a) MF to SLM I synapses is associated with an increase in supralinear summation between MF and PP synaptic inputs to SLM I; b) The increase in supralinear summation between MF and PP synaptic inputs to SLM I after LTP at MF to SLM I synapses is due to an increase in Ca 2+ currents mediated by the T/R channel subtype; and c) The increase in supralinear summation between MF and PP synaptic inputs to SLM I after LTP at MF to SLM I synapses is blocked by inhibition of protein kinases in the postsynaptic cell.